Reduced transfusion requirements during major hepatic resection with use of intraoperative isovolemic hemodilution

We report a 3-month-old girl with Costello syndrome complicating fatal hypertrophic obstructive cardiomyopathy. She had typical findings of this syndrome, slight dyspnea and persistent wheezing. Doppler echocardiography revealed asymmetric septal hypertrophy and systolic anterior movement of the anterior mitral leaflet. There was grade 1 mitral regurgitation. Although once her heart failure had been controlled medically, she died suddenly following deterioration of her heart condition. Costello syndrome can complicate fatal hypertrophic obstructive cardiomyopathy.     

Benchmarking the perioperative process: III. Effects of regional anesthesia clinical pathway techniques on process efficiency and recovery profiles in ambulatory orthopedic surgery

STUDY OBJECTIVES: (1) To incorporate regional anesthesia options for common outpatient orthopedic surgery into clinical pathways; (2) to use the clinical pathway format and the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as management tools to measure postoperative same-day surgery processes and discharge outcomes; and (3) to determine the effects of general, regional, and combined general-regional anesthesia on these processes and outcomes. DESIGN: Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathway existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. SETTING: Ambulatory surgery center in a teaching hospital. MEASUREMENTS AND MAIN RESULTS: The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients selected general anesthesia (+/- femoral nerve block) or epidural anesthesia, after which the remainder of the perioperative anesthesia process was standardized with respect to the drugs and equipment used. 1995-1996 patients did not necessarily have a choice in anesthesia technique and did not have a standardized perioperative anesthetic course with respect to specific drugs and supplies. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by anesthesia technique used, were measured. Combined general-regional anesthesia care for ACLR in 1996-1997, when compared with general anesthesia alone, led to increased pharmacy and materials costs and increased turnover time. However, patients with the combined technique showed improved recovery profiles and lower unexpected admission rates, and they required fewer nursing interventions for common postoperative symptoms. Patients receiving epidural anesthesia showed discharge outcomes similar to those patients receiving general anesthesia with femoral nerve block. Postanesthesia care unit bypass (fast-tracking) was more likely in clinical pathway regional anesthesia patients, when compared with the clinical pathway general anesthesia used. CONCLUSIONS: Clinical pathway regional anesthesia care for outpatient orthopedics may have a significant role in simultaneously containing costs and improving both process efficiency and patient outcomes.     

Imidazole binding to horse metmyoglobin: dependence upon pH and ionic strength

A series of substituted chalcone oxides (1,3-diphenyl-2-oxiranyl propanones) and structural analogs was synthesized to investigate the mechanism by which they inhibit soluble epoxide hydrolases (sEH). The inhibitor potency and inhibition kinetics were evaluated using both murine and human recombinant sEH. Inhibition kinetics were well described by the kinetic models of A. R. Main (1982, in Introduction to Biochemical Toxicology, pp. 193-223, Elsevier, New York) supporting the formation of a covalent enzyme-inhibitor intermediate with a half-life inversely proportional to inhibitor potency. Structure-activity relationships describe active-site steric constraints and support a mechanism of inhibition consistent with the electronic stabilization of the covalent enzyme-inhibitor intermediate. The electronic effects induced by altering the ketone functionality and the para-substitution of the phenyl attached to the epoxy C1 (i.e., the alpha-carbon) had the greatest influence on inhibitor potency. The direction of the observed influence was reversed for the inhibitory potency of glycidol (1-phenyl-2-oxiranylpropanol) derivatives. Recent insights into the mechanism of epoxide hydrolase activity are combined with these experimental results to support a proposed mechanism of sEH inhibition by chalcone oxides.     

Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31

Distal myopathy refers to a heterogeneous group of disorders in which the initial manifestations are weakness and atrophy of the hands and feet. We report a family segregating an autosomal dominant distal myopathy, with multiple affected individuals in whom vocal cord and pharyngeal weakness may accompany the distal myopathy, without involvement of the ocular muscles. To our knowledge, this pedigree displays a distinct distal myopathy with the added features of pharyngeal and vocal cord dysfunction (VCPDM) that has not been previously reported. We mapped the MPD2 gene for VCPDM to chromosome 5q within a 12-cM linkage interval between markers D5S458 and D5S1972 in a large pedigree (a maximum LOD score of 12.94 at a recombination fraction of 0 for D5S393) and combined genome screening and DNA pooling successfully adapted to fluorescent markers. This technique provides for the possibility of fully automated genome scans.     

Operative treatment of carpal tunnel syndrome in Denmark. Results of a questionnaire

The aim of our study was to determine the incidence of operative treatment for carpal tunnel syndrome in Denmark and to see whether there was a consensus about the place of preoperative electromyography and nerve conduction studies. A questionnaire was mailed to all surgical departments (n = 70) and all registered private surgical practices (n = 214) in Denmark. The incidence of operation was about 0.61 per 1,000 population. Most surgeons used preoperative electromyograms and nerve conduction studies in less than 50% of cases. The use of preoperative testing was related to the surgical speciality.     

Acquisition of word-object associations by 14-month-old infants

The following experiments were designed to determine the age at which infants can first readily learn word--object pairings with only minimal exposure and without social or contextual support. To address this question, 8- to 14-month-old infants were tested on their ability to form word--object associations in a "switch" design. Infants were habituated to 2 word--object pairings and then tested with 1 trial that maintained a familiar word--object pairing and 1 that involved a familiar word and object in a new combination. Across 6 experiments, only 14-month-old infants formed word--object associations under these controlled testing conditions but appeared to do so only when the objects were moving. Although 8- to 12-month-olds did not form the associations, they appeared to process both the word and the object information. These studies provide strong evidence that 14-month-old infants can rapidly learn arbitrary associations between words and objects, that this ability appears to develop at about 14 months of age, and that the Switch design is a useful method for assessing word--object learning in infancy.     

A refined kinetic analysis of plasminogen activation by recombinant bovine tissue-type plasminogen activator indicates two interconvertible activator forms

Bovine tissue-type plasminogen activator (tPA) was heterologously expressed in the methylotrophic yeast Pichia pastoris and characterized structurally and kinetically. The bovine single-chain tPA-mediated activation of bovine plasminogen was studied in the presence and absence of fibrinogen fragments. We have proposed a refined new method of kinetic analysis which allows examination of both stationary and prestationary phases of this process. The investigation revealed the presence of two interconvertible forms of the recombinant bovine tPA being in equilibrium at a 1 to 50 ratio. Only the minor form was able to bind and activate plasminogen. Saturation of the whole pool of tPA required high plasminogen concentration (Km >/= 5 microM) in order to reverse the equilibrium between the two forms. Fibrinogen fragments activated the single-chain tPA due to preferential binding and stabilization of the minor "active" form of the enzyme until all the molecules of tPA were converted. The same mechanism could be applied to human tPA as well. The Km values, obtained for recombinant bovine and human tPA in the presence of fibrinogen fragments, were found to be similar (Km = 0.1 microM) while kcat of human tPA was 5-10 times higher.     

Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen

Cross-reactivity with environmental antigens has been postulated as a mechanism responsible for the induction of autoimmune disease. Experimental autoimmune encephalomyelitis is a T cell-mediated autoimmune disease model inducible in susceptible strains of laboratory animals by immunization with protein constituents of myelin. We used myelin proteolipid protein (PLP) peptide 139-151 and its analogues to define motifs to search a protein database for structural homologues of PLP139-151 and identified five peptides derived from microbial Ags that elicit immune responses that cross-react with this self peptide. Exposure of naive SJL mice to the cross-reactive environmental peptides alone was insufficient to induce autoimmune disease even when animals were treated with Ag-nonspecific stimuli (superantigen or LPS). However, immunization of SJL mice with suboptimal doses of PLP139-151 after priming with cross-reactive environmental peptides consistently induced experimental autoimmune encephalomyelitis. Furthermore, T cell lines from mice immunized with cross-reactive environmental peptides and restimulated in vitro with PLP139-151 could induce disease upon transfer into naive recipients. These data suggest that expansion by self Ag is required to break the threshold to autoimmune disease in animals primed with cross-reactive peptides.